USP3 stabilizes p53 protein through its deubiquitinase activity

p53 is the guardian of the genome integrity and the degradation of p53 protein is mediated by MDM2. Here we report that USP3 interacts with p53 and regulates p53 stability. Depletion of USP3 lead to accelerated degradation of p53 in normal cells thereby enhanced cell proliferation and transformation. Reconstitution of wildtype USP3, but not the USP3 C168S mutant, restored the stability of p53 protein and inhibited cell proliferation and transformation. These findings suggest that USP3 is an important regulator of p53 and regulates normal cell transformation. •USP3 is a deubiquitinase for p53 and antagonizes Mdm2.•USP3 stabilizes p53 protein under normal condition.•Loss of USP3 accelerates cell proliferation and transformation.